Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Humans ; Blast Crisis/genetics* ; Leukemia, Promyelocytic, Acute/genetics* ; Oncogene Proteins, Fusion/genetics* ; Tretinoin

Aim To investigate the effect of chlorogenic acid (CGA) on chronic inflammatory pain induced by complete Freund's adjuvant (CFA) and to observe the influence of CGA on CFA-induced synaptic expression of AMAP receptor in spinal dorsal horn. Methods CFA was injected intraplantarly into the hindpaws of mice to induce mechanical allodynia and thermal hyperalgesia. The changes of paw withdrawal threshold (PWT) and the paw withdrawal latency (PWL) were tested after intrathecal administration of CGA. Meanwhile, the synaptic expression and phosphorylation of AMPA receptor subunit were assessed by immunoblot-ting. Results The intrathecal injection of CGA produced dose-depended improvement of both PWT and PWL in CFA injected mice. A higher dose of CGA (200ng) did not influence the base thresholds of normal mice. The median dose of CGA (100 ng) effectively reversed the CFA-induced synaptic expression of GluAl; meanwhile, it suppressed the phosphorylation of GluAl at Ser845, with no influence on phosphorylation at Ser831. Conclusions CGA might exert its analgesic effect by specifically inhibiting the phosphorylation of GluAl -Ser845 and the synaptic incorporation of GluAl-containing AMPA receptor.

Objective To study the use of preoperative indocyanine green retention test at 15 minutes (ICG R15) in the prediction of liver functional reserve in patients with hilar cholangiocarcinoma (HCCA).Methods The clinical data of 62 patients with HCCA treated in our department from March 2016 to March 2018 was reviewed.The relationship between preoperative ICG R15 and postoperative hepatic insufficiency was analyzed.The relationship between preoperative ICG R15 and Child-Pugh scoring was also studied.Univariate analysis was used to evaluate the risk factors of postoperative liver dysfunction.Logistic regression was used to assess the independent risk factors of postoperative liver dysfunction.The regression equation between independent risk factors and postoperative liver dysfunction was established.Results Among the 62 patients,ICG R15 was less than 10.0％ in 26 patients,between 10.0％ and 19.0％ in 17 patients,between 20.0％ and 29.0％ in 9 patients,between 30.0％ and 39.0％ in 5 patients,and over 40.0％ in 5 patients.There were 29 patients with a Child-Pugh A grading and 33 patients with a Child-Pugh B grading in the preoperative evaluation of liver function.The Wilcoxon W rank sum test was used to compare the preoperative ICG R15 in patients with Child-Pugh grading A and B separately.The ICG R15 in Child-Pugh grading A patients was significantly lower than those in Child-Pugh B grading patients (P ＜0.05).There were no significant differences in age,gender,history of previous liver diseases,duration of operation,and intraoperative blood loss (P ＞ 0.05) between the normal liver function group and the liver dysfunction group.However,there was a significant difference in the preoperative ICG R15 and preoperative bilirubin levels (P ＜ 0.05) between the two groups.The preoperative ICG R15 and preoperative bilirubin levels were significant risk factors of postoperative hepatic insufficiency.Regression analysis suggested that preoperative ICG R15 level was an independent risk factor of postoperative hepatic insufficiency (P ＜ 0.05).A regression equation:logit(P) =0.185 × preoperative ICG R15-3.152 could be constructed.Conclusions ICG R15 is an ideal clinical indicator for evaluation of preoperative liver functional reserve in patients with HCCA.It predicted the recovery of postoperative liver function.

Biomarkers ; urine ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; pathology ; urine ; Enzyme-Linked Immunosorbent Assay ; Hepatitis A Virus Cellular Receptor 1 ; metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; urine ; Kidney Diseases ; pathology ; urine ; Lipocalin-2 ; urine ; Membrane Proteins ; urine ; Sialoglycoproteins ; urine ; Tissue Inhibitor of Metalloproteinase-2 ; urine

Paeoniflorin (PAE) is the most abundant compound in Xuebijing injection widely used to treat sepsis. We aimed to investigate effect of PAE on expression of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in a rat model of sepsis. Wistar rats were divided into Normal, Model, and PAE groups (n=20 each). Endotoxin was administrated at 5 mg/ml/kg in Model and PAE rats to establish rat sepsis model. 1 h after endotoxin administration, PAE was administrated at 4 ml/kg in PAE group once per day for 3 days. Routine blood tests and biochemical indexes were assessed, including aspartate aminotransferase (AST) and creatine kinase-MB (CK-MB). The plasma sTREM-1 level was measured using quantitative ELISA. At the end of experiment, the small intestine, liver, kidney and lung were subjected to pathological examinations. A rat model of sepsis-induced multiple organ dysfunction syndrome (MODS) was established successfully with endotoxin administration (5 mg/ml/kg), evidenced by histo-pathological examinations, routine blood tests and biochemical indexes: platelet count decreased and white blood cell count increased (p<0.05), CK-MB and AST increased (p<0.05). PAE treatment significantly reduced the plasma levels of AST, CK-MB, and sTREM-1, compared to Model group (p<0.05). Meanwhile, sepsis-induced damages in the liver, lung, stomach and intestinal mucosa were also markedly ameliorated by PAE treatment. PAE demonstrated a significantly protective effect in a rat model of sepsis by decreasing plasma sTREM-1 level, reducing inflammation, preventing MODS and protecting organ functions.
Animals ; Aspartate Aminotransferases ; Creatine ; Enzyme-Linked Immunosorbent Assay ; Hematologic Tests ; Inflammation ; Intestinal Mucosa ; Intestine, Small ; Kidney ; Leukocyte Count ; Liver ; Lung ; Models, Animal ; Multiple Organ Failure ; Plasma ; Platelet Count ; Rats* ; Rats, Wistar ; Sepsis ; Stomach

OBJECTIVETo investigate the best choice of operation opportunity and operation plan for limb fractures combined with severe craniocerebral trauma in children.

METHODSFrom January 2005 to July 2012,36 patients with limb fractures and severe craniocerebral trauma were received,including 24 males and 12 females aged from 1 to 13 years old (mean, 6.1 +/- 3.0). The time from injury to hospital was (18.0 +/- 15.0) h. Glasgow coma score were less than 8 with an average of 6.4 +/- 1.3. AIS-ISS score were 25.9 +/- 8.1. Thirteen patients were open fracture, 23 were closed fracture. Patients were divided into immediate operation group (21 patients) received fracture fixation with 24 h, the average time was (15.0 +/- 7.4) h, and delayed operation group (15 patients) received fracture fixation after 24 h, the average time was (165.4 +/- 114.6) h. All patients were treated by open reduction, and 33 cases by internal fixation, 3 cases were external fixation. Operative time, blood loss, fracture healing time and brain trauma,physical trauma, postoperative rehabilitation situation were observed and evaluated.

RESULTSAll patients were healed at stage I ,and no dead, aggravating of coma, disorders of breathing and circulation occurred during operation. Operative time,blood loss,healing time in immediate operation group was (44.5 +/- 25.3) min, (47.1 +/- 36.5) ml, (2.7 +/- 0.5) months, respectively; while in delayed operation group was (87.0 +/- 40.0) min, (112.7 +/- 67.5) ml, (3.8 +/- 1.2) months,respectively; and there were obvious differences between two groups. There was no siginificant meaning in Glasgow coma score and Fugl-Meyer motor function between immediate operation group (4.7 +/- 0.6, 97.9 +/- 2.7) and delayed operation group (4.7 +/- 0.5, 97.7 +/- 3.9) (t = 0.23, P > 0.05; t = 0.11, P > 0.05).

CONCLUSIONThe condition of limb fractures combined with severe craniocerebral trauma in children is seriously, comfortable surgical opportunity should according to particular case, and immediate operation can performed on the condition of stabled vital signs.

Adolescent ; Child ; Child, Preschool ; Craniocerebral Trauma ; surgery ; Extremities ; injuries ; surgery ; Female ; Follow-Up Studies ; Fracture Fixation ; Fracture Fixation, Internal ; Fractures, Open ; surgery ; Humans ; Infant ; Male

Objective:To investigate the best choice of operation opportunity and operation plan for limb fractures com-bined with severe craniocerebral trauma in children. Methods:From January 2005 to July 2012,36 patients with limb frac-tures and severe craniocerebral trauma were received,including 24 males and 12 females aged from 1 to 13 years old (mean, 6.1±3.0). The time from injury to hospital was(18.0±15.0) h. Glasgow coma score were less than 8 with an average of 6.4±1.3. AIS-ISS score were 25.9±8.1. Thirteen patients were open fracture ,23 were closed fracture. Patients were divided into imme-diate operation group (21 patients) received fracture fixation with 24 h,the average time was (15.0±7.4) h,and delayed oper-ation group(15 patients) received fracture fixation after 24 h,the average time was(165.4±114.6) h. All patients were treated by open reduction,and 33 cases by internal fixation,3 cases were external fixation. Operative time,blood loss,fracture healing time and brain trauma,physical trauma,postoperative rehabilitation situation were observed and evaluated. Results:All pa-tients were healed at stageⅠ,and no dead,aggravating of coma,disorders of breathing and circulation occurred during opera-tion. Operative time,blood loss,healing time in immediate operation group was (44.5±25.3) min,(47.1±36.5) ml,(2.7±0.5) months,respectively;while in delayed operation group was(87.0±40.0) min,(112.7±67.5) ml,(3.8±1.2) months,respective-ly;and there were obvious differences between two groups. There was no siginificant meaning in Glasgow coma score and Fugl-Meyer motor function between immediate operation group (4.7±0.6,97.9±2.7) and delayed operation group (4.7±0.5,97.7± 3.9)(t=0.23,P>0.05;t=0.11,P>0.05). Conclusion:The condition of limb fractures combined with severe craniocerebral trau-ma in children is seriously,comfortable surgical opportunity should according to particular case,and immediate operation can performed on the condition of stabled vital signs.

The N gene and genome promoter nucleotide sequence of a Chinese Peste des petits rumiants virus (PPRV) ("China/Tib/Gej/07-30") was firstly determined. The length of N gene was 1689 nucleotides with a single open reading frame (ORF). The nucleotide and deduced amino acid sequence was compared with the homologous region of other PPRV isolates. The nucleotide sequence of the "China/Tib/Gej/07-30" was 91.7%-97.6% identical to other PPRV isolates, while a homology of 94.9%-98.5% could be observed at the amino acids level. The N gene encoded a protein of 525 amino acids. Several sequence motifs were identified on the basis of conservation in the PPRVs and the morbilliviruses. The genome length of promoter region was 107 nucleotides with 91.8%-98.2% identity to other PPRV isolates. Phylogenetic analysis showed that the "China/Tib/Gej/07-30" belonged to the Asian lineage.
Amino Acid Sequence ; Animals ; Base Sequence ; China ; Female ; Genome, Viral ; Goat Diseases ; virology ; Goats ; Molecular Sequence Data ; Nucleocapsid Proteins ; chemistry ; genetics ; Peste-des-Petits-Ruminants ; virology ; Peste-des-petits-ruminants virus ; chemistry ; classification ; genetics ; isolation & purification ; Phylogeny ; Promoter Regions, Genetic ; Sequence Alignment ; Sequence Analysis